Interactions cellule/matrice et propriétés élastiques des gros troncs artériels

Abstract

Les propriétés mécaniques des parois artérielles dépendent des cellules musculaires lisses, et des contenus en collagène et en élastine de la média. L’organisation spatiale de ces différents éléments est en partie réglée par les interactions entre les protéines d’adhérence de la matrice extracellulaire et les intégrines à la surface des cellules. La transmission des signaux mécaniques prend son origine au niveau des plaques denses ou hémi-desmosomes, composées de protéines du cytosquelette liées aux protéines d’adhérence de la matrice extracellulaire par les intégrines. Chez le rat spontanément hypertendu la fibronectine en excès semble contribuer à protéger la paroi artérielle contre les dégats mécaniques. Au cours de l’athérome, l’organisation initiale de la plaque s’accompagne de surproduction de la matrice extracellulaire, alors qu’aux stades ultérieurs la priorité revient à l’adhérence par l’intermédiaire des intégrines, prévenant la rupture de la plaque. Le rôle des intégrines dans le fonctionnement de la paroi artérielle semble majeur mais reste à ce jour encore mal connu.

The effects of increased large arteries stiffness are an elevation of pulse pressure and the development of left ventricular hypertrophy, both considered as cardiovascular risk factors independent of mean arterial pressure. The mechanical properties of the arterial wall depends not only on the smooth muscle cells, elastin and collagen contents but also on the way these components are spatially organized within the media, a process which may be regulated by extracellular matrix adhesion proteins and their cell surface integrin receptors. Interactions between vascular smooth muscle cell (VSM) and the extracellular matrix (ECM) play an important role on cell differentiation and signal transduction pathways induced by the ECM components. Mechanisms that link cytoskeletal and signalling molecules to integrins have been recently subject of intensive investigation. From a mechanical point of view, a central role could be attributed to the dense plaque which belongs to the cell-matrix adherent junctions. Dense plaques are composed of associated cytoskeletal proteins, vinculin, talin, paxilin and tensin linked to ECM proteins via integrin receptors. Molecular interactions in dense plaque are regulated by aggregation, conformational changes, phosphorylation and mechanical forces. Expression of integrins in normal and pathological vessels are relatively unexplored. In human hypertension, the hypertrophy of the arterial wall is accomplished without change in its intrinsic elastic properties assessed by the incremental elastic modulus. Aortic fibronectin expression is increased in spontaneously hypertensive rats (SHR). By increasing the cell-matrix attachments, fibronectin may contribute to protect the arterial wall components of SHRs against mechanical deterioration, for instance rupture of elastin fibers, through an increase in the maximum acceptable circumferential wall stress. In atherosclerotic vessels, matrix production might be seen in the earlier stages of atherosclerotic plaque formation, whereas the converse might be true of the latter stages when adhesion is vital in the prevention of plaque rupture. The integrin role is underestimated nevertheless it can play an important function in the stability of the plaque. Further studies using confocal microscopy, and specific anti-integrin monoclonal antibodies are needed to determine their precise role in the mechanical properties of large arteries. If we can better understand the role of integrins activation and conformational modifications with other adhesion molecules, it will be possible to modulate their function and thus intervene at the very basis of human vascular disease. [References: 36]